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We report that maternal supplementation with trans-vaccenic acid (TVA), the predominant naturally occurring trans-fatty acid in human breast milk, promoted neonatal T cell development in mice. Neonates fed by mothers on a TVA-enriched diet showed an expanded na\u00efve cluster of differentiation 4 (CD4\n                    <jats:sup>+<\/jats:sup>\n                    ) T cell population and enhanced adaptive immunity against infection. TVA reprogrammed neonatal na\u00efve CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells through a G protein\u2013coupled receptor\u2013CCCTC-binding factor axis and promoted T helper cells (Th1)\u2013skewing by cooperating with the transcription factor TBX21. Early-life exposure to maternal TVA via breastfeeding supported long-lasting antiviral immunity in adulthood. Our findings establish the multifaceted benefits of maternal nutrition and breastfeeding via TVA in promoting infant immune homeostasis and protective immunity.\n                  <\/jats:p>","DOI":"10.1126\/science.aea4041","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T18:03:22Z","timestamp":1781805802000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":3,"title":["Maternal trans-vaccenic acid shapes neonatal T cell development and early-life immune imprinting"],"prefix":"10.1126","volume":"392","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5245-9698","authenticated-orcid":true,"given":"Hao","family":"Fan","sequence":"first","affiliation":[{"name":"Department of Medicine, The University of Chicago, Chicago, IL, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhong","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Chemistry, The 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